Process for preparing soluble, sporicidally active solid polyglyoxals



Patented Mar. 5, 1953 3,079,985 PROCESS FOR PREPARING SOLUBLE, SPORHCID-ALLY ACTIVE SOLID POLYGLYUXALS Werner Richard Boehme, Somerville, andEdwin Thomas Chinery, Middlesex, N1, assignors to Ethicon, Inc, a

corporation of New Jersey No Drawing. Filed Sept. 29, 1959, Ser. No.843,055

6 Claims. (Cl. 159-48) This invention relates to a novel, solidpolyglyoxal product and to methods for its preparation.

Glyoxal, otherwise known as oxaldehyde of the empirical formula C H O iscommercially available in the form of an aqueous solution which iscolorless. This solution, as well as the glycol addition compound ofglyoxal, are both stable but the anhydrous monomeric compoundpolymerizes rapidly even at a low temperature. The commerciallyavailable solution is a 30% concentration (aqueous) containingapproximately 7% to 18% ethylene glycol and lesser amounts offormaldehyde, glycollic acid and formic acid.

Although certain forms of solid polyglyoxal are known and methods fortheir preparation are described in the literature, none of the knownmethods lend themselves readily or economically to the preparation of asolid form from the commercial solution. Thus, prolonged vacuumevaporation of aqueous glyoxal solution requires close temperaturecontrol to avoid overdrying and results in the formation of insolublepolymers or polymers of lowered solubility. The efiect of prolongedapplication of heat also causes some degradation and the loss of activeglyoxal.

in the copending application of Pepper et al., filed September 29, 1959,Serial Number 843,297, now abandoned, which is a continuation-in-part ofapplication Serial No, 692,581, filed October 28, 1957, now abandoned,both of which Serial No. 79,966, filed January 3, 1961, now U.S. Patent3,016,328, is a continuation in part there are described varioussporicidally active compositions comprising glyoxal, an alkali metalsalt and 70% isopropanol. Although these compositions are extremelyactive against a variety of spores and thus lend themselves readily touse in cold sterilization techniques, the instability of glyoxal inliquid form, i.e., aqueous or hydroalcoholic solutions, presentscommercial ditliculties with respect to marketing of the above-mentionedsporicidal compositions. Thus, it becomes apparent that if a solid,stable form of glyoxal could be made cheaply from the commercialproduct, it would be possible to make the sporicidal compositionavailable to the consumer in such a way that, by simple admixture of thedry glyoxal with isopropanol and an alkali metal salt, a sporicidallyactive composition could be made ready for use.

During the course of our investigations for the discovery of a method oftransforming commercially available glyoxal into a solid, stable form,conversion by means of direct spray-drying was attempted withoutsuccess. This is likely due to the fact that the ethylene glycol whichis present in the commercial glyoxal interferes with the spray-dryingprocess because of its hygroscopicity.

We have now discovered that commercially available glyoxal containingethylene glycol as an impurity can be readily spray-dried into adesirable, stable, substantially dry form by conducting the spray-dryingprocedure in th presence of an alkali metal salt of a carbonate orbicarbonate such as for example, sodium carbonate, potassium carbonate,sodium bicarbonate or potassium bicarbonate. The inclusion of suchalkali metal carbonates or bicarbonates in the spray-drying processpermits the material to be spray-dried into a dry form which is verysoluble in water and in 70% isopropanol. If desired, de-

tergent additives may be incorporated into the feed materials toincrease the solubility of the alkali metal salt in isopropanol and toincrease the penetration and activity of the final sporicidal solutionon surgical instruments such as forceps and scissors where the hingesurfaces are ditficult to sterilize or where dry blood may be present.Examples of such additives are solid polyalkyleneglycols, ile,polyethyleneglycol or polypropyleneglycol such as Carbowax 4000 whichmay be added in concentrations of 10% to of the contained glyoxal,preferably from about 20% to about 50%.

The concentration of added alkali metal carbonate or bicarbonate may befrom about 10% to about 100% of the weight of contained glyoxal,preferably from about 30% to about 50% In conducting the spray-dryingprocedure, the employment of proper temperatures is critical.Temperatures of the inlet air of the spray-dryer may vary from F. to 400F., preferably 200 F. to 300 F., and of the outlet air from 100 F. to280 F., preferably from 150 F. to 200 F.

As a specific example of the method which may be used for thepreparation of the novel solid glyoxal of this invention, a solution of150 parts by weight of sodium bicarbonate in 1000 parts by volume ofcommercial 30% glyoxal solution is spray-dried into a conical spraydryer at an inlet temperature of 300 F. and an outlet air temperature of215 F. The resulting product is a light cream-colored powder containing41.2% glyoxal. As another example, a solution of 150 parts of potassiumbicarbonate in 1000 parts by volume of commercial 30% glyoxal solutionis spray-dried at an inlet temperature of 2'00 F. and an outlet airtemperature of 150 F. The product is a cream-colored powder containing37.8% glyoxal.

in actual practice the solid, stable form of glyoxal of this inventionis added, in a quantity of from about 1.0 to about 5, preferably fromabout 2.0 to about 3.0 parts by weight to 100 parts by volume of 70%isopropanol. The resulting composition is capable of killing anaerobicbacterial spores after a period of three hours in fluid thioglycollatemedium, and aerobic bacterial spores, in a period of one to four hours,as shown by growth in eugon broth.

The final product obtained in accordance with the novel process of thisinvention is a glyoxal polymer containing, in physical admixture, aquantity of the particular alkali metal carbonate or bicarbonateemployed during the spray-drying procedure together with free glycol,formic acid in the form of its salt, and 2,3-dihydroxydioxane. Theproduct is white to cream in color, is in the form of amorphous hollowspheres and is freely soluble in water and hydroalcoholic solutions.

Although our novel process is particularly useful for the preparation ofa solid, stable glyoxal polymer from commercially available glyoxal,that is to say, an aqueous glyoxal solution containing ethylene glycolas an impurity, it also lends itself to the preparation of substantiallydry, solid glyoxal from substantially pure aqueous glyoxal solutions.For example, if one directly spray-dries a pure aqueous solution ofglyoxal, the resulting product is a dense material which is very slowlysoluble in water. However, if one adds to the spray-drying process asmall quantity of an alkali metal carbonate or bicarbonate, as forexample, from about 0.05% to about 1%, preferably from about 0.1% toabout 0.5%, of potassium or sodium carbonate or bicarbonate, theresulting product is a fluffy powder which is readily soluble in waterand hydroalcoholic solutions as opposed to the former which has a highdensity and is difficultly soluble in water. in this modification of ourprocess, the limits of inlet air temperature and outlet air temperaturemay be the same as those em- Table I Thioglycollate broth Eugonbroth-Hours Hours u i l se s -i i r ff Control** growth.

() =no growth.

(*)=spray-dried pre aratiou (")=3.3 ml. of 30 commercial liquid glyoxalsolution and 0.5% sodium bicarbonate in 100 ml. of 70% isopropanol.

It is to be understood that spray-drying methods described herein arenot intended to be limited to any particular mechanism, device or meansof efiecting drying through spray techniques. Any suitable means may beemployed to accomplish the physical transition, including well-known,commercially available spray-drying devices, it being only important,insofar as this invention is concerned, to maintain the propertemperature conditions and to include in the spray mixture the additivesnecessary to eifect the desired result.

What is claimed is:

l. The process of preparing a dry, solid glyoxal product which comprisesthe step of spray-drying an aqueous solution of glyoxal containingethylene glycol at an inlet air temperature of from about 150 F. toabout 400 F. and an outlet air temperature of at least less than theinlet air temperature, an amount of from about 10% to about of thecontained glyoxal of an alkali metal salt being incorporated therein.

2. The process as set forth in claim 1 wherein the alkali metal salt issodium bicarbonate.

3. The process as set forth in claim 1 wherein the alkali metal salt ispotassium bicarbonate.

4. The process of preparing a dry, solid glyoxal prodnot which comprisesthe step of spray-drying a pure aqueous glyoxal solution at an inlet airtemperature of from about F. to about 400 F. and an outlet airtemperature of at least 50 less than the inlet air temperature fromabout 0.05% to about 1% of the contained glyoxal of an alkali metal saltbeing incorporated therein.

5. The process as set forth in claim 4 wherein the alkali metal salt ispotassium bicarbonate.

6. The process as set forth in claim 4 wherein the alkali metal salt issodium bicarbonate.

References Cited in the file of this patent UNITED STATES PATENTS2,018,797 Lewis Oct. 29', 1935 FOREIGN PATENTS 653,588 Great Britain May16, 1951 OTHER REFERENCES Weissberger: Technique of Organic Chemistry,vol. H1 (1950), page 626.

1. THE PROCESS OF PREPARING A DRY, SOLID BLYOXAL PRODUCT WHICH COMPRISESTHE STEP OF SPRAY-DRYING AN AQUEOUS SOLUTION OF GLYOXAL CONTAININGETHLYENE GLYCOL AT AN INLET AIR TEMPERATURE OF FROM ABOUT 150*F. TOABOUT 400*F. AND AN OUTLET AIR TEMPERATURE OF AT LEAST 50* LESS THAN THEINLET AIR TEMPERATURE, AN AMOUNT OF FROM ABOUT 10% TO ABOUT 100% OF THECONTAINED GLYOXAL OF AN ALKALI METAL SALT BEING INCORPORATED THEREIN.